The objective of this proposal is to explore the biologic and clinical significance of frequent herpes simplex virus (HSV) reactivation in persons infected with the human immunodeficiency virus (HIV) both in terms of transmission and pathogenesis of HIV. Serologic evidence of HSV is common in persons with HIV, by the clinical relevance has not been adequately studied. Our preliminary data suggests that HSV reactivities in most HIV-infected persons at a rate 10 times greater than HIV-negative persons, 60% of reactivation are subclinical, and that HIV-infected pregnant women reactivate HSV at delivery up to 8 times more often than HIV-negative women. Further, HIV can be detected on rectal mucosal surfaces in 22% of subjects with frequent HSV2 reactivation. These observations, if validated, have implications for the sexual and perinatal transmission of HIV and HSV. The specific aims of this proposal related to this long-term objective are to 1) To evaluate the significance of symptomatic and subclinical HSV reactivation in HIV-infected persons, including third trimester pregnant women, and identify a group of patients at high risk for transmission of HSV during periods of asymptomatic reactivation. 2) To identify what mucosal interactions occur between HIV and HSV as they relate to potential for transmission of HIV.